Oxygen Uptake Efficiency Slope Predicts Poor Outcome In Patients With Idiopathic Pulmonary Arterial Hypertension

Objects:Cardiopulmonary exercise testing(CPET)can evaluate subject’ s heart and lung functions objectively,quantitatively and comprehensively.Oxygen uptake efficiency slope(OUES),an submaximal parameter obtained from CPET,can predict the prognosis of patients with left heart failure.Whether OUES can independently predict prognosis in patients with idiopathic pulmonary arterial hypertension(IPAH)is unknown.Our study sought to evaluate whether OUES can independently predict mortality and clinical worsening in patients with IPAH.Methods:Patients with newly diagnosed IPAH who underwent symptom-limited cardiopulmonary exercise testing(CPET)at baseline during the period November 2010 to June 2015 in our hospital were prospectively enrolled.Patients were followed regularly,clinical worsening,mortality and lung transplantation were recorded during the following period.Multiple linear regression analysis was performed to assess the association between OUES and independent variables,which included age,gender,body surface area(BSA)and body mass index(BMI).Correlations between two variables were explored using either the Pearson or Spearman correlation coefficient as appropriate.Receiver-operator characteristic(ROC)curve analysis was used to identify the area under the curve and the cutoff point for parameters associated with clinical worsening and survival.Prognostic value was assessed by survival curves(Kaplan-Meier method)as well as uni-and multivariate Cox analyses.Results:1.Two hundred ten patients were identified with IPAH and underwent CPET.159 patients were women,the mean age was 32±10 years.The mean pulmonary vascular resistance(PVR)was 12.6 ± 6.3 Wood units and the mean cardiac index(CI)was 2.8±0.8 L·min-1·m-2.The median duration of follow-up was 41 months.During the follow-up period,31 patients died,1 patient underwent lung transplantation,and 85 patients presented with clinical worsening.2.Multivariate linear regression analysis showed that OUES only increased linearly with BSA(R = 0.40,P<0.0001).The mean value of OUES was 0.94 ± 0.3 and the mean value of OUESI(OUES/BSA)was 0.57 ± 0.17 m-2.The mean values of OUES and OUESI were significantly decreased as the worsen of WHO function classes(all P<0.0001).OUESI was significantly correlated with peak VO2/kg(r = 0.79,P<0.0001),VE/VCO2 slope(r =-0.75,P<0.0001),CI(r = 0.42,P<0.0001),and PVR(r =-0.51,all P<0.0001).3.On univariate analysis,WHO-FC,NT-proBNP and variables obtained from right heart catheterization(RHC)and CPET,except for age and gender,were all significant predictors of mortality and lung transplantation.On multivariate analysis,the results showed that NT-proBNP(x2:9.88,HR 95%CI:1.001(1.000-1.001),P<0.002)and OUESI(x2:8.66,HR 95%CI:0.99(0.99-0.99),P<0.003)were independently predictive of mortality and lung transplantation.4.Patients with OUESI ≤ 0.52 m-2 had a worse 5-year survival rate than patients with OUESI>0.52 m-2(41.9%versus 89.8%,P<0.0001),after adjustment for age,gender and body mass index,the hazard ratio with 95%CI was 7.94(3.22-19.60).5.On univariate analysis,WHO-FC,NT-proBNP and variables obtained from right heart catheterization(RHC)and CPET,except for age and gender,were also all significant predictors of clinical worsening.On multivariate analysis,the results showed that OUESI(x2:26.54,HR 95%CI:0.99(0.99-0.99),P<0.0001)and CI(x2:7.23,HR 95%CI:0.62(0.44-0.88),P<0.007)were independently predictive of clinical worsening.6.Patients with OUESI≤0.62 m-2 had a worse 5-year clinical worsening-free rate than patients with OUESI>0.62 m-2(17.6%versus 83.5%,P<0.0001),after adjustment for age,gender and body mass index,the hazard ratio with 95%CI was 7.23(3.48-15.04).Conclusions:The OUES,a submaximal parameter obtained from CPET,provides excellent prognostic information for predicting clinical worsening,mortality and lung transplantation in patients with IPAH.